Diuretics are not for lymphedema

Because of the incredible lack of awareness and/or knowledge of lymphedema in the medical community, it is very common to hear of lymphedema patients speak of being prescribed diuretics (water pils) by their physcians in attempting to treat this condition.

It is important to understand not only that diuretics are not for lymphedema, but to understand why.

The long term use of diuretics will eventually lead to a serious worsening of lymphedema and will help set the stage for increased complications such as tissue fibrosis.

Hopefully, this page will clear up questions regarding this and will help patients better manage their lymphedema.

Diuretics Definition

A class of drugs or other substance that promotes the formation and release of urine. Diuretics are used to decease the fluid volume in the treatment of many underlying medical conditions. Most people commonly call diuretics a “water pill.”

Anything that promotes the formation of urine by the kidney. (The word “diuretic” comes from a combination of the Greek “dia-”, thoroughly + “ourein”, to urinate = to urinate thoroughly).

Diuresis may be due to a huge number of causes including metabolic conditions such as diabetes mellitus (in which the increased glucose level in the blood causes water to be lost in the urine); substances in food and drink (such as coffee, tea, and alcoholic beverages); and specific diuretic drugs.

All diuretic drugs – which are usually called, more simply, diuretics – cause a person to “lose water” but they do so by diverse means, including:

Inhibiting the kidney's ability to reabsorb sodium, thus enhancing the loss of sodium in the urine. And when sodium is lost in the urine, water goes with it. (This type of diuretic is called a high-ceiling diuretic or a loop diuretic).

Enhancing the excretion of both sodium and chloride in the urine so that water is excreted with them. This is how the thiazide diuretics work.

Blocking the exchange of sodium for potassium, resulting in excretion of sodium and potassium but relatively little loss of potassium. These diuretics are therefore termed potassium sparing diuretics.
Some diuretics work by still other mechanisms. And some diuretics have other effects and uses such as in treating hypertension. (3)

Lymphedema or Edema?

To understand why these agents are not recommended for the treatment of lymphedema we must first start with a basic definition of edema and lymphedema.

Diuretics are used to assist in the correction of the base problem causing the edema.

Lymphedema: A disorder in which “lymph” collects usually in a limb as a result of a congenital, hereditary malformation of the lymphatic system, or is a result secondary conditions such as node removal for biopsies, damage to the lymphatics from radiation, injury or trauma or by parasitic infection. Diuretics cannot help the underlying condition of lymphedema.

Why not use diuretics for lymphedema?

Perhaps the single most important consideration is in the composition of the lymph fluid caused by lymphedema. The fluid i a protein-rich substance that provides a breeding and nourishment center for bacteria. This has to be removed to lesson the risks of cellulitis and lymphangitis.

This fluid also has to be removed so as to prevent the formation and progression of fibrosis as lymphedema advances through the various stages.

Diuretics remove none of this waste fluid as it is a heavier molecule fluid then just water itself..

Diuretics and Lymphedema

A question that came up is whether diuretics should be used in the treatment of lymphedema. In my opinion, the answer is usually no. There are some exceptions and I will explain.

Diuretics are one of the best treatments for patients suffering from edema of the legs due to congestive heart failure. When the right side of the heart does not work efficiently, the pressure in the venous system increases and this, in turn, results in increased pressure in the tissues and edema results. The edema is not from the lymphatic system and is not lymphedema.

Diuretics, such as lasix, cause the kidney to eliminate water from the blood. This in turn reduces the pressure in the venous system and allows the edema to drain into the venous system. Unfortunately, when someone drinks additional water the fluid and edema returns and so many patients require fluid and salt restriction to have the best results. Diuretics must be given regularly to eliminate as much water from the blood system as possible and control the edema. In some case, even when high doses of diuretics are given, the edema cannot be controlled by drugs alone and compression garments can be of additional benefit for these patients. The lymphatic system can be completely normal and patients will still develop edema due to congestive heart failure.

The lymphatic system drains through the lymph nodes and lymphedema generally arises due to an obstruction in the lymphatic system. This can occur due to surgery, radiation or trauma. Decreasing the pressure in the venous system by removing water from the venous system does not help reduce lymphedema. In fact, patients with normal cardiac function do not have excess tissue edema. As a result, fluid removed by diuretics must be replaced by oral intake to maintain a normal fluid balance and any reduction in fluid due to diuretics in normal people is temporary. Diuretics have no value for the treatment of lymphedema in patients who do not have edema due to congestive heart failure or other similar conditions.

A patient could have a mixed condition where lymphedema is complicated by edema due to congestive heart failure. These patients may benefit from treatment with diuretics because of the mixed condition. Check with your doctor to see if you have some component of edema.

Dr. Mortimer addressed this question in a recent publication in Angiology 48:87-91, 1997. He said,

“Lymphedema, regardless of etiology, is essentially incurable but different therapy approaches exist which serve to contain swelling. The objectives of treatment are to reduce swelling, restore shape, and prevent inflammatory episodes, eg, recurrent cellulitis. There are essentially three main approaches to lymphedema treatment: physical therapy, drug therapy, and surgery. Any edema arises from an imbalance between capillary filtration and lymph drainage. The principle of physical therapy is to a) reduce excessive capillary filtration and b) improve drainage of interstitial fluid and macromolecules from congested regions to normally draining lymph node sites. This is achieved through a combination of compression, exercise, and if possible, massage. Control of recurrent inflammatory episodes can only be achieved through diabetic type skin care, a reduction in swelling, and if necessary, prophylactic antibiotics. Drug therapy comprises diuretics or the coumarin/flavonoid group of drugs. The use of diuretics for pure lymphedema is physiologically unsound but may be of use in edema of mixed origin and in palliative (cancer) circumstances.”

Diuretics, Benzopyrones and Lymphedema

Diuretics

Diuretics (“water pills”) are medications that removes excess water from your whole body. But they are generally NOT recommended for treating lymphedema. That's because they don't eliminate the protein that attracts and hangs onto the extra lymph fluid. Once you stop taking the medicine, the protein pulls the fluid back to your arm, and it swells up again.

It's best to first try treatments that specifically deal with your arm, and not your whole body. An occasional use of a diuretic before a special event, like an outdoor wedding, is not unreasonable.

On the other hand, you might have to use diuretics if you have certain medical conditions that cause general swelling throughout the body. These conditions include high blood pressure, congestive heart failure, or general edema.

Taking diuretics requires a doctor's supervision. Regular use of a diuretic also requires regular blood tests to make sure there is no problem with your blood chemistry.

Benzopyrones

Benzopyrones are used in Europe to treat lymphedema, but the Food and Drug Administration has not approved these drugs for use in the United States.

Coumarin is the most commonly used benzopyrone. (Don't confuse it with Coumadin, a blood thinner.) The manufacturer claims the drug helps to “eat up” proteins in stagnant lymphatic fluid, reducing both the water and the swelling. Therapists who use it say it can take weeks, maybe years, to experience the drug's benefits.

Diuretics and Lymphedema

Excerpt - Norton School of Lymphatic Therapy

Diuretics, often prescribed, usually make the lymphedema worse. Diuretics are able to draw off the water content of the edema while the protein molecules remain in the tissue spaces. These proteins continue to draw water to the edematous areas as soon as the diuretic loses its effectiveness. These accumulated proteins also lead to a higher concentration of proteins in the edema fluid and cause the tissues to become even more fibrotic and indurated. Benzopyrones for lymphedema have been tried for many years, primarily in other countries. Their therapeutic effect as it relates to lymphedema continues to be debated. Furthermore, the product lacks FDA approval. Some patients who have used the drug here in the United States have discontinued its use after having experienced adverse side effects.

Examples of diuretics

furosemide, Lasix - commonly used diuretic (trade name Lasix) used to treat hypertension and edema

indapamide, Lozal - diuretic (trade name Lozal) used in the treatment of hypertension

mannitol, Osmitrol - a diuretic (trade name Osmitrol) used to promote the excretion of urine

thiazide - any of a group of drugs commonly used as diuretics in the treatment of hypertension; they block the reabsorption of sodium in the kidneys

Uses for diuretics

Doctors prescribe certain diuretics to prevent, treat or improve symptoms in a variety of conditions, such as:

High blood pressure

Congestive heart failure

Edema

Polycystic ovary syndrome

Certain kidney disorders, such as kidney stones

Diabetes insipidus

Female hirsutism

Osteoporosis

Heart failure

By flushing excess fluids from the body, diuretics can relieve the edema (swelling from excess fluids) that commonly occurs with heart failure. Specifically, spironolactone and eplerenone have been independently shown to benefit patients with heart failure, thus reducing the workload on the heart. Most patients with heart failure are treated with a loop diuretic, in addition to a low sodium diet. In addition, spironolactone or eplerenone may be added to increase the drug's effectiveness and reduce the loss of potassium often caused by diuretics. It is important for any patients taking diuretics for heart failure to have their electrolyte levels carefully monitored. Heart failure patients who are prescribed diuretics will often be on the medications for the rest of the lives.

Renal insufficiency. A condition in which the kidneys are unable to function normally. Diuretics can sometimes worsen this condition.

Types of Diuretics

There are several types of diuretics.

The categories are defined based upon their mechanism of action.

a.Osmotic Diuretics.

Osmostic diuretics produce a diuresis of water rather than a diuresis of sodium. The body does not metabolize osmotic diuretics. Instead, the drug molecules are not reabsorbed in the kidney tubules. This greatly affects the tonicity of every part of the kidney tubules through which the glomerular filtrates pass. By the process of osmosis, the drug molecules draw an increased amount of water from the interstitial fluid compartment. The result is that a great volume of urine is produced (water diuresis). It just so happens that sodium is contained in that urine and is subsequently removed from the body. Thus, the osmotic diuretics indirectly produce a removal of sodium from the body. Following is one example of an osmotic diuretic: Mannitol. Mannitol is used to prevent acute renal (kidney) failure, evaluate kidney functioning, treat glaucoma (by the reduction of intraocular pressure), promote the urinary excretion of toxic substances (diuresis in certain drug intoxications) and reduce intracranial pressure (pressure in the head). The usual dosage of mannitol is from 50 to 200 grams in a 24-hour period by intravenous infusion. Side effects associated with the use of mannitol include pulmonary congestion, fluid and electrolyte imbalance, acidosis, electrolyte loss, and dryness of mouth and dehydration. Since mannitol may crystallize on exposure to low temperatures, you should observe mannitol vials and premixed bags for such crystals. When you observe these crystals, you should warm the vials or bags in a 500° C water bath in order to dissolve the crystals. The product should be cooled to body temperature before the mannitol solution is administered. Mannitol is available in a 5, 10, 15, 20, and 25 percent injection.

b.Thiazide Diuretics

Thiazide diuretics work by the inhibition of sodium reabsorption in the first portion of the distal tubule. The passive diffusion of the accompanying water and chloride is correspondingly reduced. Thus, the result is an increased excretion of sodium, water, and chloride from the body. When the thiazide acts on the proximal tubule, the carbonic anhydrase activity in the distal tubule is also decreased. This causes increased secretion of potassium. Consequently, the water lost contains sodium, potassium, and chloride. This loss of potassium can present problems to the patient.

(1) Hydrochlorothiazide (Hydrodiuril®). Hydrochlorothiazide is used in the treatment of essential hypertension and edema found in congestive heart failure. The usual dose of this drug is from 12.5 to 100 milligrams per day. Side effects commonly associated with hydrochlorothiazide include hypokalemia, hyperglycemia, and hyperuricemia. This drug should be used in caution in patients suffering from diabetes or gout and in patients who take digitalis.

(2) Chlorothiazide (Diuril®). This drug is used as a diuretic and as an antihypertensive. It is available in both parenteral and oral dosage forms. For side effects, refer to hydrochlorothiazide.

(3) Chlorthalidone (Hygroton®). Although chlorthalidone is not the same chemically as the thiazide diuretics, it has the same effects as these agents. For indications and side effects, you should refer to hydrochlorothiazide.

c.Potassium-Sparing Diuretics.

This type of diuretic is used when there is a need to maintain normal levels of potassium in the patient along with the diuresis. The specific mechanisms of actions of selected drugs in this category.

(1) Spironolactone (Aldactone®). Spironolactone causes sodium diuresis and potassium retention by acting as an aldosterone competitive antagonist. That is, this drug acts on the distal tubule to block the sodium-potassium exchange mechanism. The net result is sodium loss and potassium retention. Consequently, by antagonizing aldosterone, sodium as well as water diuresis and potassium retention are affected. Spironolactone is used for primary hyperaldosteronism, edema associated with congestive heart failure, cirrhosis of the liver or ascites, essential hypertension, and in hypokalemia when other means are considered inappropriate or inadequate. The usual dose of this drug is from 25 to 400 milligrams per day depending upon the condition of the patient. Although spironolactone is a mild diuretic, it can hasten major side effects such as gastrointestinal symptoms (for example: cramping and diarrhea), lethargy, hyperkalemia, and hyponatremia. Hyperkalemia is a major side effect that occurs in patients who have impaired renal function. Hyperkalemia can cause irregularities that may be fatal. Spirolactone also causes estrogen-like side effects because of its hormone-like structure.

(2) Triamterene (Dyrenium®). While triamterene produces effects similar to those of spironolactone, the effects produced by triamterene are not dependent on the presence of aldosterone. This agent acts directly on the distal tubule where it prevents the passage of sodium across the membrane of the tubule. Thus, by blocking sodium reabsorption, potassium loss is reduced. Triamterene is used for edema associated with congestive heart failure and cirrhosis of the liver. The usual dosage of this drug is from 25 to 200 milligrams per day. The daily dose should not exceed 300 milligrams. Side effects associated with this agent include electrolyte imbalances, hyperkalemia, weakness, and dry mouth. Like spironolactone, hyperkalemia is a major side effect which can occur in patients who have impaired renal function or when the drug is administered alone.

d.Carbonic Anhydrase Inhibitor Diuretics

Carbonic anhydrase inhibitors produce diuresis by inhibiting carbonic anhydrase in the renal tubules. Carbonic anhydrase is an enzyme that catalyzes the following reaction: From the reaction above, it can be deduced that removal of or blocking the enzyme carbonic anhydrase would result in a much slower reaction. Consequently, there would be a greatly reduced production of hydrogen ions and bicarbonate ions. This interferes with the ion exchange mechanism at the distal tubule, where the sodium ion that accompanies the bicarbonate ion is reabsorbed only by exchange for hydrogen or potassium ions secreted into the tubule. Normally the bicarbonate ion that accompanies the sodium ion (provided by the glomerular filtrate) is reabsorbed almost complete at the distal tubule. With reduced production of hydrogen ion due to inhibition of the carbonic anhydrase, the bicarbonate ion, together with the sodium ion will not be reabsorbed. Thus, the sodium will be excreted in an unusually large amount–with a corresponding loss of water (remember, where sodium goes, water goes).

Acetazolamide (Diamox®). Acetazolamide is one example of a carbonic anhydrase inhibitor. Although rarely used today, it may be used in the treatment of edema because of congestive heart failure; drug-induced edema; petit mal and unlocalized seizures; and open-angle and secondary glaucoma. The usual dosage of this drug ranges from 250 milligrams to 2 grams–depending on the type of condition being treated. Actually, the dosage recommendations for glaucoma and epilepsy differ considerably from those of congestive heart failure, since the first two conditions are not dependent on carbonic anhydrase inhibition in the kidney which requires intermittent dosage if it is to recover from the inhibitory effect of the therapeutic agent. The side effects of this agent include loss of appetite, transient myopia (nearsightedness), drowsiness, and acidosis. Acetazolamide is available in the injectable form.

e.Inhibition of Sodium Transport in the Ascending Limb of the Loop of Henle, the Distal Tubule, and the Proximal Sites Diuretics.

Diuretics of this type are extremely potent and rapidly acting. In fact, they are used only after less potent–but safer–diuretics have failed. As the category type states, this type of diuretic acts by inhibiting sodium transport in the ascending limb of the loop of Henle, the distal tubule, and in the proximal sites. Thus, a greater fraction of filtered sodium can escape reabsorption. Thereby, increased sodium and water excretions occur. Diuretics of this type are called “loop diuretics”.

(1) Furosemide (Lasix®). Furosemide is used in the treatment of edema associated with congestive heart failure, cirrhosis of the liver and renal disease, pulmonary edema, and hypertension. It is particularly useful when an agent with a greater diuretic potential than that of those commonly used is desired. This agent is also a rapidly acting diuretic. When administered orally it acts within one hour. When administered by injection it acts within 5-10 minutes. However, the agent does produce massive changes in electrolyte and water balance in the body. The usual dosage of furosemide is 20 to 80 milligrams given in a single dose–preferably in the morning. Depending on the patient’s response, this dose can be repeated, maintained, or reduced. There are numerous adverse effects associated with the use of furosemide.

These adverse effects include hypokalemia, hyponatremia, hyperglycemia, electrolyte depletion, and hypovolemia. Reservsible and irreversible hearing impairment and loss may occur with any of the loop diuretics. It is often associated with rapid infusion and the use of extremely high doses. The injectable form of the drug must be stored at controlled room temperature and should not be used if the solution is yellow. The oral solution and tablet preparations should be dispensed in light–resistant containers.

The mechanism of action of this type is very similar to the thiazide diuretics. That is, drugs of this category inhibit sodium and chloride reabsorption that results in the increased excretion of sodium, chloride, and water. Chlorthalidone (Hygroton®). This agent differs from the thiazide diuretics only in chemical structure. Chlorthalidone’s pharmacological action is indistinguishable from the thiazide diuretics. Chlorthalidone is used in the management of hypertension–either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in patients who have the more severe forms of hypertension. It is also used as adjunctive therapy in the treatment of edema associated with congestive heart failure, hepatic cirrhosis, and various forms of renal dysfunctions. Refer to the information on hydrochlorothiazide for side effect information.

The potassium-sparing and thiazide diuretics have different but complementary mechanisms and sites of action. Therefore, when given together they produce additive diuretic and antihypertensive effects. The thiazide component blocks the reabsorption of sodium and chloride ions and thus increases the quantity of sodium traversing the distal tubule and the volume of water excreted in the urine. This characteristically induces potassium loss. The potassium-sparing component inhibits the reabsorption of sodium in exchange for potassium and hydrogen ions at the distal tubule, so that sodium excretion is greatly favored and the excess loss of potassium, as well as hydrogen and chloride ions induced by the thiazide, is reduced.

(1) Aldactazide® (combination of spironolactone and hydrochlorothiazide). This drug is used for the treatment of edema associated with congestive heart failure, cirrhosis of the liver and ascites and for essential hypertension.

(2) Dyazide® (combination of triamterene and hydrochlorothiazide). This agent is used in the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and hypertension. The usual dosage of this product from 1 to 2 capsules taken twice daily after meals. The patient should take no more than four capsules per day. The side effects associated with this agent include hyperglycemia, hyperuricemia, and gastrointestinal disturbances. Each Dyazide® capsule contains 37.5 milligrams of triamterene and 25 milligrams of hydrochlorothiazide. There are other combinations of these diuretics available as generics or as Maxide® (75/50; 50/25). One must be very careful and doublecheck the active ingredients to ensure that the correct product is dispensed.(1)

Potential Side Effects of Diuretics

Potential side effects of diuretics

The most common side effect associated with diuretics is potassium loss. With the exception of potassium-sparing versions, all diuretics may cause a loss of potassium. Rarely, potassium-sparing diuretics can cause a build-up of potassium in the body.

Symptoms of potassium loss include:

Tiredness

Weakness

Numbness

Tingling

Muscle cramps

Constipation

Vomiting

Fast heartbeat (tachyarrhythmia)

Patients should contact their physicians if they have any of the following side effects from diuretics, most of which are related to diuresis (urinating too much) and dehydration: ·

Dry mouth

Increased thirst

Arrhythmia (abnormal heartbeat)

Confusion, mental changes or moodiness

Weak pulse

Heaviness or weakness of the legs

Dizziness or lightheadedness, especially after getting up from a sitting or lying position

Patients on diuretics should inform their physicians if they become sick, especially with severe or continuing vomiting or diarrhea. These conditions can cause the body to lose too much water and potassium.(2)

Are diuretics safe and effective for lymphedema?

No. Diuretics are not recommended for the treatment of lymphedema uncomplicated by other morbidities. Chronic diuretic use can cause electrolyte abnormalities and an overall worsening of the condition. (SOR: C, based on consensus guidelines.) Chlorothiazide is the only diuretic that has been studied.

A double-blind crossover trial from 1965 compared chlorothiazide 500 mg twice daily given 5 days each week with placebo given on the same schedule as treat¬ment for primary lymphedema. Patients with coexisting cardiac, renal, and hepatic disease were excluded. There were 27 patients, and the study lasted 28 weeks, with patients completing 14 weeks of chlorothiazide therapy followed by 14 weeks of placebo.1 The patients showed a reduction in lower limb circumference (mean 0.25 inch, P less than .01), weight loss (mean 3.0 lb, P less than .05), and subjective improvement of symp¬toms (P less than .01) while being treated with chlorothiazide. There was, however, no correlation between symptom severity and degree of improvement with treatment, and none of the cases displayed complete resolution of the lymphedema. No significant side effects from the therapy were reported.1

In 1998, the American Cancer Society sponsored a workshop on lymphedema with the purpose of developing a consensus report on the diagnosis and treatment of the condition. Although they commented that the use of diuretics was still under evaluation, the drug class did not appear helpful for lymphedema uncomplicated by other morbidities.2

Experts have noted that the high protein content in the interstitial fluid of lymphedema allows it to rapidly pull water back into the interstitium via osmotic pressure after water is removed by the diuretic.3 Diuretics themselves can cause electrolyte disturbances with chronic use, and experts believe they can also encourage increased protein accumulation and fibrosis in the tissue, which could lead to a worsened condition.4,5